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  • Title: Trimetrexate with leucovorin versus trimethoprim-sulfamethoxazole for moderate to severe episodes of Pneumocystis carinii pneumonia in patients with AIDS: a prospective, controlled multicenter investigation of the AIDS Clinical Trials Group Protocol 029/031.
    Author: Sattler FR, Frame P, Davis R, Nichols L, Shelton B, Akil B, Baughman R, Hughlett C, Weiss W, Boylen CT.
    Journal: J Infect Dis; 1994 Jul; 170(1):165-72. PubMed ID: 8014493.
    Abstract:
    Trimetrexate is a powerful inhibitor of the dihydrofolate reductase of Pneumocystis carinii. AIDS patients (n = 215) with moderate to severe P. carinii pneumonia were enrolled in a double-blind study of trimetrexate plus leucovorin versus trimethoprim-sulfamethoxazole (TMP-SMZ) for 21 days. By study day 10, study therapy failed because of lack of efficacy in 16% of patients assigned to TMP-SMZ and 27% assigned to trimetrexate (P = .064), and the PAO2-PaO2 improved significantly faster with TMP-SMZ. By study day 21, failure rates were 20% with TMP-SMZ and 38% with trimetrexate (P = .008), with respective mortality rates of 12% and 20% (P = .088). By study day 49, the difference in mortality (16% vs. 31%) was significant (P = .028). The cumulative incidence of serious and treatment-terminating adverse events including hematologic toxicities was less with trimetrexate (P < .001). Thus, trimetrexate plus leucovorin was effective, albeit inferior to TMP-SMZ, for moderately severe P. carinii pneumonia but was better tolerated than TMP-SMZ.
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